ME01950B - Inhibitori mitotskog kinezina i postupci za njihovu upotrebu - Google Patents

Inhibitori mitotskog kinezina i postupci za njihovu upotrebu

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Publication number
ME01950B
ME01950B MEP-2011-460A MEP46011A ME01950B ME 01950 B ME01950 B ME 01950B ME P46011 A MEP46011 A ME P46011A ME 01950 B ME01950 B ME 01950B
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Montenegro
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alkyl
phenyl
nrarb
membered
ora
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MEP-2011-460A
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English (en)
French (fr)
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Shelley Allen
Jeremy Hans
Eli M Wallace
Qian Zhao
Joseph P Lyssikatos
Tom Aicher
Ellen Laird
John Robinson
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Array Biopharma Inc
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Claims (25)

1. Jedinjene formule i solvati, razdvojeni enantiomeri, diastereomeri, racemske smeše i njene farmaceutski prihvatljive soli, naznačen time, što: R može da bude Z-NR2R3; gde R1 predstavlja C1-C10 alkil, C2-C10 alkenil, C2-C12alkinil, fenil, 5-7-očlani heteroaril, zasićeni ili delimično nezasićeni C3-C12 cikloalkil, zasićeni ili delimično nezasićeni 3-8-očlani heterocikloalkil, -0R3,-NR4OR5, CRb(=NORc), C(=O)Ra, ili -NR4R5 gde su pomenuti alkil, alkenil, alkinil, fenil, heteroaril, cikloalkil, i heterocikloalkil koji su po slobodnom izboru supstituisani sa jednom ili više grupa nezavisno odabranih od okso (pod uslovom da nije supstituisan na pomenutoj fenil ili heteroaril),halogen, cijano, nitro, trifluorometil, difluorometil, fluorometil, fluorometoksi, difluorometoksi, trifluorometoksi, azido, -O(C=O)ORd, -NRbS02Rd, -SOgNRaRb, -G(=O)Ra, -C(=O)ORa, -OC(=O)Ra, -OCH2C(=O)ORa, -NRbC(=O)ORd, -NRbC(=O)Ra, -C(=O)NRaRb, -NRaRb, -NRQC(=O)NRaRb, -NRCC(NCN)NRaRb, -ORa, -OP(=O)(ORa)2, C1-C10 alkil, C2-C10 alkenil, C3-C12 alkinil, C3-C12 cikloalkil, fenil, 5-7- očlani heteroaril, fenil-C1-C3-alkil, 5-6- očlani heteroaril-C1-3-alkil, 3-8-o61ani heterociklil i 5-6 očlani heterociklil-C1-3-alkil; Ar1 i Ar2 su svaki za sebe fenil ili 5-7- očlani heteroaril, gde su pomenutifenil i heteroaril po slobodnom izboru supstituisani sa jednom ili više grupakoje su nezavisno odabrane od F, Cl, Br, I, cijano, nitro, C1-C10 alkil, C2-C10alkenil, C2-C12 alkinil, zasićeni ili delimično nezasićeni C3-C12 cikloalkil,zasićeni ili delimično nezasićeni 3-8- očlani heterocikloalkil, trifluorometil,difluorometil, fluorometil, fluorometoksi, difluorometoksi, trifluorometoksi, ORa, -O(C=O)ORd, -OP(=O)(ORa)(ORa), NRaRb, -NRbSO2Rd, -SO2NRaR, SR6, SOR6, S02R6, -C(=O)Ra, -C(=O)ORa, -OG(=O)Ra, -OCH2C(=O)ORa, -NRbC(=O)ORd, -NRbC(=O)Ra, -C(=O) NRaRb i -NRcC(=O)NRaRb; R2 i su svaki za sebe odabrani iz grupe koju čine vodonik, C1-C10 alkil, zasićeni ili delimično nezasićeni C3-C12Cikloalkil, aminokiselina odabrana iz grupe koju čine Ala, Arg, Asn, Asp, Cys, Glu, Gln, Gly, His, Hyl, Hyp, ne, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, Val, fosfoserin, fosfotreonin, fosfotirozin, 4-hidroksiprolin, hydroxylysine, demozin, izodemozin, gama-karboksiglutamat, hipurna kiselina, oktahidroindol-2-karboksilna kiselina, statin, l,2,3,4-tetrahidroizohinolin-3-karboksilna kiselina, penicilamin, ornitin, 3-metilhistidin, norvalin, beta-alanin, gama-aminobuterna kiselina, citrulin, homocistein, homoserin, metil-alanin, para-benzoilfenilalanin, fenilglicin, propargilglicin, sarkozin, metionin, sulfon i terc-butilglicin, i dipeptid, gde su pomenuti alkil i cikloalkil po slobodnom izboru supstituisani; gde R4 i R5 svaki za sebe predstavljaju H, trifluorometil, difluorometil, fluorometil, C1-C10 alkil, C2-C10 alkenil, C2-C12 alkinil, zasićeni ili delimično nezasićeni C3-C12 cikloalkil, zasićeni ili delimično nezasićeni 3-8-očlani heterocikloalkil, fenil ili 5-7-očlani heteroaril, gde su pomenuti alkil, alkenil, alkinil, cikloalkil, heterocikloalkil, fenil i heteroaril po slobodnom izboru supstituisani sa jednom ili više grupa nezavisno odabranih od okso (pod uslovom da nije supstituisan na pomenutoj fenil ili heteroaril), halogen, cijano, nitro, trifluorometil, difluorometil, fluorometil, fluorometoksi, difluorometoksi, trifluorometoksi, azido, -O(C=O)ORd, -NRbSOgRd, -SO2NRaRb, -C(=O)Ra, -C(=O)ORa -OC(=O)Ra, -NRbC(=O)ORd, -NRbC(=O)Ra, -C(=O)NRaRb, -NRaRb, -NRCC(=O)NRaRb, NRcC(NCN)NRaRb, -ORa, C1-C1O alkil, C2-C10 alkenil, C2-C12 alkinil, C3-C12 cikloalkil, fenil, 5-7-očlani heteroaril, fenil-Ci-C3-alkil, 5-6- očlani heteroaril-C1-3-alkil, 3-8- očlani heterocikloalkil i 5-6- očlani heterociklil-C1-3 -alkil, ili R4 i R5 zajedno sa atomima za koji su vezani grade zasićeni ili delimično nezasićeni 3-8- očlani heterociclični prsten koji može daobuhvati 1 do 3 dodatna heteroatoma, pored heteroatoma gde za koje supomenuti R4 i R5 vezani, odabrani od N, O i S, gde je pomenutiheterociklični prsten supstituisan sa jednom ili više grupa koje sunezavisno odabrane od okso, halogen, cijano, nitro, trifluorometil,difluorometil, fluorometil, fluorometoksi, difluorometoksi, trifluorometoksi, azido, -O(C=O)ORd, -NRbS02Ra, -S08NRaRb, -C(=O)Ra, -C(=O)ORa, -OC(=O)Ra, -NRbC(=O)ORd, -NRbC(=O)Ra, -C(=O)NRaRb, -NRaRb, -NRcC(=O)NRaRb, -NRcC(NCN)NRaRb, -ORa, C1-C10 alkil, C2-C10 alkenil, C2-C12 alkinil, C3-C12cikloalkil, fenil, 5-7- očlani heteroaril, fenil-C1-C3-alkil, 5-6-očlani heteroaril-C1-3-alkil, 3-8-očlani heterocikloalkil i 5-6- očlani heterociklil-C1-3-alkil; R6 je C1-C10 alkil, C2-C10 alkenil, C2-C12 alkinil, C1-C12 heteroalkil, C1-C12 heteroalkenil, C1-C12 heteroalkinil, zasićeni ili delimično nezasićeni C3-C12 cikloalkil, zasićeni ili delimično nezasićeni 3-8- očlani heterocikloalkil, fenil ili 5-7- očlani heteroaril, gde su pomenuti alkil, alkenil, alkinil, heteroalkil, heteroalkenil, heteroalkonol, cikloalkil, heterocikloalkil, fenil i heteroaril po slobodnom izboru supstituisani sa jednom ili više grupa nezavisno odabranih od okso (pod uslovom da nije supstituisan na pomenutoj fenil ili heteroaril), halogen, cijano, nitro, trifluorometil, difluorometil, fluorometil, fluorometoksi, difluorometoksi, trifluorometoksi, azido, -O(C=O)ORd, -NRbSO2Rd, -SO2NRaRb, -C(=O)Ra, -C(=O)ORa, -OC(=O)Ra, -NRbC(=O)ORd -NRbC(=O)Ra, -C(=O)NRaRb, -NRaRb, -NRcC(=O)NRaRb, -NR°C(NCN)NRaRb, -ORa, C1-C10 alkil, C2-C10alkenil.C2-C12 alkinil, C3-C12 cikloalkil, fenil, 5-7-očlani heteroaril, fenil-C1-C3-alkil, 5-6- očlani heteroaril-C1-3-alkil, 3-8-očlani heterocikloalkil i 5-6- očlani heterociklil-C1-3-alkil; gde je Ra vodonik, trifluorometil, C1-C10 alkil, C2-C10 alkenil, C2-C12 alkinil, zasićeni ili delimično nezasićeni C3-C12 cikloalkil, cikloalkilalkil, fenil, arilalkil, 5-7- očlani heteroaril, 5-6- očlani heteroaril-C1-3-alkil, 3-8-očlani heterocikloalkil ili zasićeni ili delimično nezasićeni 5-6- očlani heterociklil- C1-3-alkil, gde su pomenuti alkil, alkenil, alkvnil, cikloalkil, cikloalkilalkil,fenil, arilalkil, heteroaril, heteroarilalkil, heterocikloalkil i heterociklilalkilpo slobodnom izboru supstituisani sa jednom ili više grupa koje sunezavisno odabrane od okso (pod uslovom da nije supstituisan napomenutoj fenil ili heteroaril)), halogen, cijano, nitro, trifluorometil,difluorometil, fluorometil, fluorometoksi, difluorometoksi, trifluorometoksi, azido, -O(C=O)ORl1, -NEflSOaE11, -SOgNRPltf, -C(=O)Re, -C(=O)ORe,- OC(=O)Re, -NRfC(=O)ORh, -!TIlfC(=O)Re, -C(=O)NReR;, -NReRf, -NRgC(=O)NReR;, -NRcC(NCN)NReRf, -ORe, d-Cio alkil, C2-C10 alkenil, C3-C12 alkinil, C3-Cig oikloalkil, fenil, 5-7- očlani heteroaril, fenil-Ci-G3-alkil, 5-6-očlani heteroaril-Ci-3-alkil, zasićeni ili delimično nezasićeni 3-8 - očlani heterocikloalkil i 5-6- očlani heterociklil-Ci-3-alkil; gde su Rb, R°, E/ i Rč svaki za sebe nezavisno vodonik ili Ci-Cio alkil, ili Ra i Rb zajedno sa atomom za koji su spojene grade 4 do 10- očlani zasićeni ili delimično nezasićeni heterociklični prsten koji može da obuhvati od 1 do 3 dodatna heteroatoma, osim atom azota za koji su pomenuti Ra i Rb spojeni, koji su odabrani od N, 0 i S; gde su Rd i BP- svaki za sebe trifluorometil, Ci-Cio alkil, zasićeni Hi delimično nezasićeni C3-Ci2 cikloalkil, fenil, fenil-Cl-C3-alkil, 5-7- očlani heteroaril, 5-6- očlani heteroaril-Ci-3-alkil, zasićeni ih' delimično nezasićeni 3-8- očlani heterocikloalkil ili 5-6- očlani heterociklil-Ci-3-alkil; gde je Revodonik, trifluorometil, C1-C10 alkil, C2-C10 alkenil, C2-C12 alkinil, zasićeni ili delimično nezasićeni C3-Ci2Cikloalkil, C3-Ci2Cikloalkil-Ci-3-alkil, fenil, fenil-Ci-C3-alkil, 5-7- očlani heteroaril, 5-6- očlani heteroaril-Cl-3-alkil, zasićeni ili dehinično nezasićeni 3-8- očlani heterocikloalkil ih" 5-6-očlani heterocikhl-Cl-3-alkil; i gde Z predstavlja alkilen sa 1 do 6 atoma ugljenika, ili alkenilen ih" alkinilen gde svaki ima od 3 do 6 atoma ugh'enika, gde su pomenuti alkilen, alkenilen i alkinilen po slobodnom izboru supstituisani sa jednom ih više grupa koje su nezavisno odabrane izmedju okso, halogen, cijano, nitro, trifluorometil, difluorometil, fluorometil, fluorometoksi; difluorometoksi, trifluorometoksi, azido, -0(C=0)ORd, - NRtS02Rd, -SO2NRaRb, -C(=O)Ra,-C(=O)ORa, -OC(=O)Ra, -NRbC(=0)ORd, - NRtC(=O)Re, -C(=O)NRaRb, -NRaRb, -NRcC(=O)NRaRb, -0Ra, Ci-C10alkil,C2-C10 alkenil, C2-C12 alkinil, C3-C12Cikloalkil, fenil, 5-7-očlani heteroaril, fenil-C1- C3-alkil, 5-6-očlani heteroaril-C1-3-alkil, 3-8-očlani heterocikloalkil i 5-6- očlani heterociklil-C1-3-alkil.
2. Jedinjenje iz patentnog zahteva 1, naznačen time, što R1 predstavlja - NR4OR5.
3. Jedinjenje iz patentnog zahteva 2, naznačen time, što su R4 i R5 svaki za sebe odabrani od grupe koju čine H, C1-C10 alkil, zasićeni ili delimično nezasićeniC3-C12 cikloalkil, i 5-7- očlani heteroaril.
4. Jedinjenje iz patentnog zahteva 1, naznačen time, što R1 može da bude C1-C10 alkil, C3-C12 cikloalkil, 3-8- očlani heterocikloalkil, O-C1-C10alkil, ORa, fenil, 5-7- očlani heteroaril, CRb(=NORc), ili C(=O)Ra, gde su pomenuti alkil, cikloalkil, heterocikloalkil, fenil i heteroaril po slobodnom izboru supstituisani sa jednom ili više grupa nezavisno odabranih od ORa, NRaRb, halogen, C3-C12Cikloalkil, C1-C10alkil, fenil i CF3.
5.Jedinjenje iz patentnog zahteva 1, naznačen time, što je Ar1 supstituisani ili nesupstituisani fenil, tienil, imidazohl, piridil, ili pirazohl.
6. Jedinjenje iz patentnog zahteva 5, nazančen time, što je Ar1 po slobodnom izboru supstituisan sa jednom ili više grupa koje su nezavisno odabrane od F, Cl, Br, I, ORa, NRaRb, NO2, CN, C(=O)ORa C1-C10 alkil, i CF3.
7. Jedinjenje iz patentnog zahteva 6, naznačen time, što je Ar2 supstituisani ili nesupstituisani fenil, tienil, imidazolil, piridil, ili pirazolil.
8. Jedinjenje iz patentnog zahteva 7, naznačen time, što su Ar1 i Ar2 pos slobodnom izboru supstituisani sa jednom ili više grupa koje su nezavisno odabrane od F, Cl, Br, I, ORa, NRaRb, N02, CN, C(=O)ORa C1-C10 alkil, i CF3.
9. Jedinjenje iz patentnog zahteva 1, predstavljeno formulom gde: Rx i Ry svaki za sebe predstavljaju H, C1-C10 alkil, zasićeni ili delimično nezasićeni C3-C12 cikloalkil ili fenil, gde su pomenuti alkil, cikloalkil i fenil po slobodnom izboru supstituisani sa jednom ili više grupa koje su nezavisno odabrani od okso (pod uslovom da nije došlo do supstitucije na pomenutoj fenil grupi), halogen, cijano, nitro, trifluorometil, difluorometil, fluorometil, fluorometoksi, difluorometoksi, trifluorometoksi, azido, -O(C=O)ORd, -NRbS02Rd,- SO2NRaRb, -C(=O)Ra, -C(=O)ORa, -OC(=O)Ra, -OCH2C(=O)ORa, -NRbC(=O)ORd, -NRbC(=O)Ra -C(=O)NRaRb, -NRaRb, -NRcC(=O)NRaRb, -NRcC(NCN)NRaRb, -ORa, C1-C10 alkil, C2-C10alkenil, C2-Cl2alkinil, C3-C12 cikloalkil, fenil, 5-7- očlani heteroaril, fenil-C1-C3-alkil, 5-6- očlani heteroaril-Cl-3-alkil, 3-8- očlani heterociklil i 5-6- očlani heterociklil-Cl-3-alkil, ili Rx i Ry zajedno sa atomom za koji su spojeni grade zasićeni ili delimično nezasićeni C3-C12karbociklični prsten ili 3-8-očlani heterociklični prsten sa jednim ili više heteroatoma koji su nezavisno odabrani od N, 0 i S, gde su pomenuti karbociklični i heterociklični prstenovi po slobodnom izboru supstituisani sa jednom ili više grupa koje su nezavisno odabrane od okso, halogen, cyano, nitro, trifluorometil, difluorometil, fluorometil, fluorometoksi, difluorometoksi, trifluorometoksi, azido, -O(G=O)ORd, -NRbS02Rd, -S02NRaRb, -C(=O)Ra, -C(=O)ORa, -OC(=O)Ra, -NRbC(=O)ORd, -NRbC(=O)Ra, -C(=O)NRaRb, -NRaRb, -NRcC(=O)NRaRb, -NRcC(NCN)NRaRb, -ORa, G1-C10 alkil, C2-C10 alkenil, C2-C12 alkinil, C3-C12 cikloalkil, fenil, 5-7- očlani heteroaril, fenil-C1-C3-alkil, 5-6-očlani heteroaril-C1-3-alkil, 3-8- očlani heterocikloalkil i 5-6- očlani heterociklil-C1-3-alkil; ili Ra i Rx zajedno sa atomima za koje su vezani grade zasićeni ili delimično nezasićeni 3-8- očlani heterociklični prsten koji može da obuhvati od 1 do 3 dodatna heteroatoma, osim atoma kiseonika za koji je pomenuti Ra spojen, koji su odabrani od N, 0 i S, gde pomenuti heterociklični prsten po slobodnom izboru može da bude supstituisan sa jednom ili više grupa koje su nezavisno odabrane od okso, halogen, cijano, nitro, trifluorometil, difluorometil, fluorometil, fluorometoksi, difluorometoksi, trifluorometoksi, azido, -0(C=0)0Rh, -NRfS02Rh, -SO2NReRf, -C(=O)Re, -C(=O)ORe, -OC(=O)Re, -NRfC(=0)0Rh, -NRfC(=O)Re, -C(=O)NReRf, -NReRf, -NRgC(=0)NReRf, -NR°C(NCN)NReRf, -0Re, C1-C10 alkil, C2-G10 alkenil, C2-C12 alkinil, C3-C12Cikloalkil, fenil, 5-7- očlani heteroaril, fenil-C1-C3-alkil, 5-6-očlani heteroaril-C1-3-alkil, 3-8- očlani heterocikloalkil i 5-6- očlani heterociklil-C1-3-alkil.
10.Jedinjenje iz patentnog zahteva 9, naznačen time, što barem jedna odR* i Rv nije H.
11. Jedinjenje prema bilo kojem od patentnih zahteva 9 ili 10, naznačen time, što Ra može da bude H ili C1-C10 alkil.
12. Jedinjenje iz patentnog zahteva 11, naznačen time, što je Rx C1-C10 alkil.
13.Jedinjenje iz patentnog zahteva 1, naznačen time, stoje odabrano od: i njihovi razdvojeni enantiomeri i diastereomeri.
14. Jedinjenje iz patentnog zahteva 13, naznačen time, što ima strukturu: i njene farmaceutski prihvatljive soli.
15. Jedinjenje iz patentnog zahteva 13, naznačen time, što ima strukturu: i njene farmaceutski prihvatljive soli.
16. Jedinjenje iz patentnog zahteva 13, naznačen time, što ima strukturu: i njene farmaceutski prihvatljive soli.
17. Jedinjenje iz patentnog zahteva 13, naznačen time, što ima strukturu: i njene farmaceutski prihvatljive soli. i njene farmaceutski prihvatljive soli.
18. Jedinjenje iz patentnog zahteva 13, naznačen time, što ima strukturu:
19. Jedinjenje iz patentnog zahteva 13, naznačen time, što ima strukturu: i njene farmaceutski prihvatljive soli.
20.Farmaceutska kompozicija, naznačen time, što obuhvata jedinjenjekako je traženo prema bilo kojem od patentnih zahteva od 1 do 19 ifarmaceutski prihvatljivi nosač.
21.Jedinjenje prema bilo kojem od patentnih zahteva od 1 do 20, zaupotrebu kao leka.
22.Upotreba jedinjenja prema bilo kojem od patentnih zahteva od 1 do 20za proizvodnju leka za lečenje oboljenja kod ljudi ili životinja koji mogu dase tretiraju inhibiranjem mitoze.
23.Upotreba prema patentnom zahtevu 21, naznačen time, što je pomenuto oboljenje ih poremećaj hiperproliferativni poremećaj.
24.Upotreba prema patentnom zahtevu 22, naznačen time, što stanjenenormalnog ćelijskog rasta predstavlja kancer, autoimuno oboljenje, artritis, odbacivanje grafta, zapaljensko oboljenje creva ih" proliferaciju indukovanu nakon medicinskih procedura.
25.Upotreba prema patentnom zahtevu 21, naznačen time, stoje oboljenje ili poremećaj gljivična ili druga eukariotska infekcija.
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Families Citing this family (53)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DK1847534T3 (da) * 2001-12-11 2011-08-29 Kyowa Hakko Kirin Co Ltd Thiadiazolin-derivater til behandling af kræft
ATE537158T1 (de) 2003-04-18 2011-12-15 Kyowa Hakko Kirin Co Ltd M-stage-kinesin-inhibitor
AU2004247551A1 (en) * 2003-06-10 2004-12-23 Fuji Photo Film Co., Ltd. Thiadiazoline derivative
JP2008510013A (ja) * 2004-08-18 2008-04-03 メルク エンド カムパニー インコーポレーテッド 有糸分裂キネシン阻害剤
US7449486B2 (en) 2004-10-19 2008-11-11 Array Biopharma Inc. Mitotic kinesin inhibitors and methods of use thereof
AU2006225637A1 (en) * 2005-03-22 2006-09-28 Fuji Photo Film Co., Ltd. Therapeutic agent for hematopoietic tumor
JP5060285B2 (ja) * 2005-03-22 2012-10-31 協和発酵キリン株式会社 固形腫瘍治療剤
UA95907C2 (en) 2005-05-02 2011-09-26 Эррей Биофарма Инк. Mitotic kinesin inhibitors and methods of use thereof
WO2006137490A1 (ja) * 2005-06-24 2006-12-28 Kyowa Hakko Kogyo Co., Ltd. 再狭窄治療剤
EP2081918A2 (en) * 2006-10-03 2009-07-29 Array Biopharma, Inc. Mitotic kinesin inhibitors and methods of use thereof
WO2008070739A1 (en) * 2006-12-06 2008-06-12 Cytokinetics, Inc. Ksp activators
JP5455915B2 (ja) * 2007-10-19 2014-03-26 メルク・シャープ・アンド・ドーム・コーポレーション Ｋｓｐキネシン活性を阻害するためのスピロ縮合した１，３，４−チアジアゾール誘導体
PE20090968A1 (es) * 2007-11-09 2009-07-13 Schering Corp Compuestos para inhibir la actividad de ksp kinesina
CN104958292B (zh) * 2008-10-16 2018-10-16 阵列生物制药公司 用于在治疗中增加凋亡的有丝分裂抑制剂
US9561214B2 (en) * 2008-10-16 2017-02-07 Array Biopharma Inc. Method of treatment using inhibitors of mitosis
US20120070370A1 (en) * 2009-05-13 2012-03-22 Siddiqui M Arshad Spiro 1,3,4-thiadiazoline derivatives as ksp inhibitors
NZ601967A (en) 2010-03-12 2015-03-27 Omeros Corp Pde10 inhibitors and related compositions and methods
FR2991199B1 (fr) * 2012-05-30 2015-05-15 IFP Energies Nouvelles Procede de preparation d'un catalyseur mettant en oeuvre une etape de sechage rapide et son utilisation pour la synthese fischer-tropsch
CN104869995A (zh) 2012-08-13 2015-08-26 阵列生物制药公司 用于治疗低aag患者的癌症的arry-520
EP3030236A1 (en) 2013-08-08 2016-06-15 Array Biopharma, Inc. Filanesib combined with pomalidomide displays enhanced anti-tumor activity
CA2934617A1 (en) 2013-12-23 2015-07-02 Bayer Pharma Aktiengesellschaft Antibody drug conjugates (adcs) with kinesin spindle protein (ksp)
NZ716462A (en) * 2014-04-28 2017-11-24 Omeros Corp Optically active pde10 inhibitor
NZ716494A (en) 2014-04-28 2017-07-28 Omeros Corp Processes and intermediates for the preparation of a pde10 inhibitor
EP3233127A1 (de) 2014-12-15 2017-10-25 Bayer Pharma Aktiengesellschaft Antikörper-wirkstoff-konjugate (adcs) von ksp-inhibitoren mit aglycosylierten anti-tweakrantikörpern
CN107530313A (zh) 2015-04-24 2018-01-02 奥默罗斯公司 Pde10抑制剂以及相关组合物和方法
AU2016282723B2 (en) 2015-06-22 2021-09-23 Bayer Pharma Aktiengesellschaft Antibody drug conjugates (ADCs) and antibody prodrug conjugates (APDCs) with enzymatically cleavable groups
JP2018525334A (ja) 2015-06-23 2018-09-06 バイエル ファーマ アクチエンゲゼルシャフト キネシンスピンドルタンパク質（ｋｓｐ）阻害剤の抗ｔｗｅａｋｒ抗体との抗体薬物複合体
CN107921288A (zh) 2015-06-23 2018-04-17 拜耳医药股份有限公司 Ksp抑制剂的靶向缀合物
US11071788B2 (en) 2015-06-23 2021-07-27 Bayer Pharma Aktiengesellschaft Antibody drug conjugates of kinesin spindel protein (KSP) inhibitors with antiB7H3-antibodies
WO2017079678A1 (en) 2015-11-04 2017-05-11 Omeros Corporation Solid state forms of a pde10 inhibitor
WO2017216028A1 (en) 2016-06-15 2017-12-21 Bayer Pharma Aktiengesellschaft Specific antibody-drug-conjugates (adcs) with ksp inhibitors and anti-cd123-antibodies
WO2018114804A1 (de) 2016-12-21 2018-06-28 Bayer Pharma Aktiengesellschaft Spezifische antikörper-wirkstoff-konjugate (adcs) mit ksp-inhibitoren
KR102556826B1 (ko) 2016-12-21 2023-07-18 바이엘 파마 악티엔게젤샤프트 효소적으로 절단가능한 기를 갖는 항체 약물 접합체 (adc)
KR20210033470A (ko) 2018-06-18 2021-03-26 바이엘 악티엔게젤샤프트 효소에 의해 절단 가능한 링커 및 개선된 활성 프로파일을 갖는, cxcr5에 대해 유도된 결합제-약물 접합체
CN121712509A (zh) 2023-05-04 2026-03-20 锐新医药公司 用于ras相关疾病或病症的组合疗法
US20250049810A1 (en) 2023-08-07 2025-02-13 Revolution Medicines, Inc. Methods of treating a ras protein-related disease or disorder
IL327306A (en) 2023-10-12 2026-05-01 Revolution Medicines Inc Macrocyclic RAS inhibitors
WO2025096683A1 (en) * 2023-10-30 2025-05-08 University Of Health Sciences And Pharmacy In St. Louis Err modulators
WO2025096684A1 (en) * 2023-10-30 2025-05-08 University Of Health Sciences And Pharmacy In St. Louis Err modulators
WO2025171296A1 (en) 2024-02-09 2025-08-14 Revolution Medicines, Inc. Ras inhibitors
WO2025240847A1 (en) 2024-05-17 2025-11-20 Revolution Medicines, Inc. Ras inhibitors
WO2025255438A1 (en) 2024-06-07 2025-12-11 Revolution Medicines, Inc. Methods of treating a ras protein-related disease or disorder
WO2025265060A1 (en) 2024-06-21 2025-12-26 Revolution Medicines, Inc. Therapeutic compositions and methods for managing treatment-related effects
WO2026006747A1 (en) 2024-06-28 2026-01-02 Revolution Medicines, Inc. Ras inhibitors
WO2026015796A1 (en) 2024-07-12 2026-01-15 Revolution Medicines, Inc. Methods of treating a ras related disease or disorder
WO2026015801A1 (en) 2024-07-12 2026-01-15 Revolution Medicines, Inc. Methods of treating a ras related disease or disorder
WO2026015825A1 (en) 2024-07-12 2026-01-15 Revolution Medicines, Inc. Use of ras inhibitor for treating pancreatic cancer
WO2026015790A1 (en) 2024-07-12 2026-01-15 Revolution Medicines, Inc. Methods of treating a ras related disease or disorder
WO2026050446A1 (en) 2024-08-29 2026-03-05 Revolution Medicines, Inc. Ras inhibitors
WO2026072904A2 (en) 2024-09-26 2026-04-02 Revolution Medicines, Inc. Compositions and methods for treating lung cancer
WO2026090116A2 (en) 2024-10-21 2026-04-30 Revolution Medicines, Inc. Ras inhibitors
US20260108528A1 (en) 2024-10-22 2026-04-23 Revolution Medicines, Inc. Methods of treating a ras protein-related disease or disorder
WO2026090245A1 (en) 2024-10-22 2026-04-30 Revolution Medicines, Inc. Use of ras inhibitors for treating cancer

Family Cites Families (53)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2702803A (en) * 1954-04-12 1955-02-22 Lilly Co Eli Substituted heterodiazoles
SU1065410A1 (ru) * 1982-05-07 1984-01-07 Днепропетровский Ордена Трудового Красного Знамени Химико-Технологический Институт Им.Ф.Э.Дзержинского Способ получени 2-амино-5-трет-алкил-1,3,4-тиадиазолов
ATE72431T1 (de) * 1985-08-31 1992-02-15 Fisons Plc 5-gliedrige heterocyclische angiotensinumwandlungsenzym-inhibitoren.
US4762072A (en) * 1986-10-07 1988-08-09 Westinghouse Electric Corp. Desk and space dividing wall panel assembly
GB8625774D0 (en) 1986-10-28 1986-12-03 Reckitt & Colmann Prod Ltd Thiadiazole derivative
JPH0572686A (ja) 1991-09-11 1993-03-26 Konica Corp ハロゲン化銀写真感光材料
WO1993022311A1 (en) 1992-04-27 1993-11-11 E.I. Du Pont De Nemours And Company Fungicidal 1,3,4-oxadiazines and 1,3,4-thiadiazines
US6159938A (en) * 1994-11-21 2000-12-12 Cortech, Inc. Serine protease inhibitors comprising α-keto heterocycles
WO1996023769A2 (en) * 1995-02-02 1996-08-08 Smithkline Beecham Plc Heterocyclic compounds possessing 5ht2c receptor antagonist activity
US5958957A (en) * 1996-04-19 1999-09-28 Novo Nordisk A/S Modulators of molecules with phosphotyrosine recognition units
US5668159A (en) * 1996-05-08 1997-09-16 The Dupont Merck Pharmaceutical Company 1,3,4-thiadiazoles and 1,3,4-oxadiazoles as IIb/IIIa antagonists
HRP980093A2 (en) 1997-02-28 1998-12-31 Lilly Co Eli Heterocyclic compounds, pharmaceutical compositions comprising same, and methods for inhibiting "beta"-amyloid peptide release and/or its synthesis by use of such compounds
ES2216338T3 (es) * 1997-12-16 2004-10-16 Warner-Lambert Company Llc Aminas novedosas como agentes farmaceuticos.
US6235762B1 (en) * 1998-11-23 2001-05-22 American Cyanamid Company 2-aryl-Δ2-1,3,4-(oxa and thia)diazoline insecticidal and acaricidal agents
JP2000159756A (ja) 1998-11-23 2000-06-13 American Cyanamid Co ２―アリ―ル―δ２―１，３，４―（オキサおよびチア）ジアゾリン殺虫および殺ダニ剤
GEP20032999B (en) * 1999-01-13 2003-06-25 Warner Lambert Co 1-Heterocycle Substituted Diarylamines
US6281217B2 (en) * 1999-03-25 2001-08-28 Dingwei Tim Yu Class of piperazino substituted thiazoles
US6545004B1 (en) * 1999-10-27 2003-04-08 Cytokinetics, Inc. Methods and compositions utilizing quinazolinones
WO2001056994A1 (en) 2000-02-04 2001-08-09 Biogen, Inc. Integrin antagonists
WO2003018008A1 (en) * 2000-02-25 2003-03-06 Shionogi & Co., Ltd. Apo ai expression accelerating agent
DK1847534T3 (da) * 2001-12-11 2011-08-29 Kyowa Hakko Kirin Co Ltd Thiadiazolin-derivater til behandling af kræft
AU2003249597B2 (en) * 2002-03-08 2007-06-28 Merck Sharp & Dohme Corp. Mitotic kinesin inhibitors
AU2003246551A1 (en) 2002-06-25 2004-01-06 Dieter Borner Assembly for recording the use of rds radio receivers
US7294643B2 (en) * 2002-11-22 2007-11-13 Board Of Regents, The University Of Texas System UK-1 analogues: methods of preparation and use
US20050004186A1 (en) 2002-12-20 2005-01-06 Pfizer Inc MEK inhibiting compounds
US20040167188A1 (en) * 2003-02-14 2004-08-26 Zhili Xin Protein-tyrosine phosphatase inhibitors and uses thereof
ATE537158T1 (de) * 2003-04-18 2011-12-15 Kyowa Hakko Kirin Co Ltd M-stage-kinesin-inhibitor
US7115642B2 (en) * 2003-05-02 2006-10-03 Rigel Pharmaceuticals, Inc. Substituted diphenyl isoxazoles, pyrazoles and oxadiazoles useful for treating HCV infection
US7326790B2 (en) * 2003-05-02 2008-02-05 Rigel Pharmaceuticals, Inc. Diphenylisoxazole compounds and hydro isomers thereof
EP1628666B1 (en) * 2003-05-14 2015-09-23 NeuroGenetic Pharmaceuticals, Inc. Compouds and uses thereof in modulating amyloid beta
WO2004110351A2 (en) * 2003-05-14 2004-12-23 Anadys Pharmaceuticals, Inc. Heterocyclic compounds for treating hepatitis c virus
US7220745B2 (en) 2003-05-15 2007-05-22 Rigel Pharmaceuticals Heterocyclic compounds useful to treat HCV
US20050009877A1 (en) * 2003-05-15 2005-01-13 Henry Lu Methods of identifying HCV NS5B polymerase inhibitors and their uses
WO2004111023A1 (ja) 2003-06-10 2004-12-23 Kyowa Hakko Kogyo Co., Ltd. チアジアゾリン－１－オキシド誘導体
AU2004247551A1 (en) 2003-06-10 2004-12-23 Fuji Photo Film Co., Ltd. Thiadiazoline derivative
EP1671957A4 (en) * 2003-10-10 2007-03-14 THIADIAZOLINDERIVATE
JP2005232016A (ja) 2004-02-17 2005-09-02 Kyowa Hakko Kogyo Co Ltd オキサジアゾリン誘導体
GB0406867D0 (en) 2004-03-26 2004-04-28 F2G Ltd Antifungal agents
JP2008510013A (ja) * 2004-08-18 2008-04-03 メルク エンド カムパニー インコーポレーテッド 有糸分裂キネシン阻害剤
US7449486B2 (en) 2004-10-19 2008-11-11 Array Biopharma Inc. Mitotic kinesin inhibitors and methods of use thereof
FR2876586B1 (fr) 2004-10-20 2007-10-12 Persee Medica Composition pour prevenir ou traiter le stress, notamment les bouffees de stress chronique et permanent
JP2006265107A (ja) * 2005-03-22 2006-10-05 Kyowa Hakko Kogyo Co Ltd 緑内障治療剤
AU2006225637A1 (en) * 2005-03-22 2006-09-28 Fuji Photo Film Co., Ltd. Therapeutic agent for hematopoietic tumor
JP5060285B2 (ja) * 2005-03-22 2012-10-31 協和発酵キリン株式会社 固形腫瘍治療剤
JP2008137893A (ja) * 2005-03-22 2008-06-19 Kyowa Hakko Kogyo Co Ltd 関節炎治療剤
JP2008150291A (ja) * 2005-03-22 2008-07-03 Kyowa Hakko Kogyo Co Ltd 乾癬治療剤
UA95907C2 (en) 2005-05-02 2011-09-26 Эррей Биофарма Инк. Mitotic kinesin inhibitors and methods of use thereof
WO2006137490A1 (ja) * 2005-06-24 2006-12-28 Kyowa Hakko Kogyo Co., Ltd. 再狭窄治療剤
EP2081918A2 (en) 2006-10-03 2009-07-29 Array Biopharma, Inc. Mitotic kinesin inhibitors and methods of use thereof
TWI411395B (zh) 2007-12-24 2013-10-11 Syngenta Participations Ag 殺蟲化合物
US9561214B2 (en) 2008-10-16 2017-02-07 Array Biopharma Inc. Method of treatment using inhibitors of mitosis
CN104869995A (zh) 2012-08-13 2015-08-26 阵列生物制药公司 用于治疗低aag患者的癌症的arry-520
EP3030236A1 (en) 2013-08-08 2016-06-15 Array Biopharma, Inc. Filanesib combined with pomalidomide displays enhanced anti-tumor activity

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